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Blood simple
Oct 11th 2007
From The Economist print edition
Because they lack an essential component,
blood transfusions may be killing some of the
people they are intended to save
IF THERE were any sure bets in medicine, you might think that “bloodtransfusions save lives” would be one of them. But there aren't. Even thoughdeaths caused in the 1980s by accidental HIV infection mean that donatedblood is now screened meticulously to keep it free of infectious agents, there isstil a nagging feeling that something is wrong.
In 2004, for instance, Sunil Rao of Duke University Medical Centre, in NorthCarolina, carried out a study of people suffering from acute coronary syndrome(a specific type of heart attack). One conclusion that could be drawn from hisresearch was that unnecessary blood transfusions might be causing tens ofthousands of deaths in America alone. Dr Rao found that patients who had hada transfusion because of a low red blood-cel count had an 8% chance of dyingwithin 30 days. Without a transfusion, only 3% died. Those numbers need tobe treated with caution. As Dr Rao points out, the patients who underwenttransfusion were, on average, sicker and older than those who did not.
Nevertheless, his study is not the only indication of something amiss.
In recent years, research has suggested that transfusion is not necessarily a good thing for patients suffering from serious injuries, for those who haveundergone surgery and even for those who are anaemic. And a study carriedout earlier this year found that critically ill children whose red blood-cell countshad dropped by half fared no better after a transfusion than those who did notreceive one.
As a result of al this, questions are being asked about whether somethinghappens to blood when it is banked that causes it to stop working properly.
What that might be has remained a mystery. But it may be one no longer. Agroup of Dr Rao's col eagues, led by Jonathan Stamler, think the answer is agas cal ed nitric oxide — or, rather, a lack of it.
Out of gas
The main reason for giving a patient blood is that it carries oxygen. It carrieslots of other things, too, such as glucose. But it is a lack of oxygen that will killyou quickest. However, as Dr Stamler points out, what determines whethertransfused blood works as a treatment is not merely how much oxygen it iscarrying, but whether that oxygen can reach the tissues that need it. This iswhere nitric oxide comes in.
Nitric oxide increases the flow of blood to tissues by dilating the arteries thatpenetrate those tissues. The best known example is the erectile tissue of thepenis (Viagra works by sustaining the signal that the gas gives). However, it isnot just penile blood vessels that nitric oxide relaxes. When a red blood cellreaches any tissue in need of oxygen it releases nitric oxide in order to dilatethe capillaries. Only then can it deliver its cargo. And that is doubly true of thecel s in stored blood since red blood cel s become less flexible with age, andthus less able to squish into capil aries. Dr Stamler thus wondered if a lack ofnitric oxide was causing the problems associated with transfusions.
What he and his col eagues discovered, and published this week in theProceedings of the National Academy of Sciences, was that the amount of nitricoxide in stored blood does indeed decrease — and does so rapidly. Within a dayof storage, blood loses 70% of its nitric oxide. After a few days, up to 90% hasbeen lost.
A second paper in the same journal, by Dr Stamler's col eague TimothyMcMahon, confirmed this result (in fact, it showed that the initial drop ofaround 70% happens within three hours of col ection) and showed that it wasnot caused by the way blood is processed, but merely by the passage of time.
Dr McMahon also established that stored blood does indeed lose its ability todilate blood vessels.
Dr Stamler is in little doubt about the significance of these findings.
Furthermore, he warns that putting blood lacking nitric oxide into the bodydoes not merely dilute what gas is already present in the bloodstream. Bloodthat is poor in nitric oxide wil scavenge the gas from other tissues, causing thevessels in those tissues to constrict. If the tissue in question is heart muscle,the result will be a heart attack.
These papers, therefore, make a strong case that a lack of nitric oxide iscreating the problems with transfusions — though as Michael Strong, thepresident of the American Association of Blood Banks, points out, they do notsettle the issue once and for al . That would require a proper, randomisedclinical trial.
And therein lies the rub. Because blood transfusion is such an old practice (itdates back to 1818) it has never been subjected to modern clinical standards.
Nobody is questioning whether car-crash victims, say, should havetransfusions after massive blood loss. Without it they would undoubtedly die.
But for those not threatened with exsanguination it is far less clear whether atransfusion is a good idea. There are no rules about when to transfuse and whoto do it to. These are matters of judgment, and knowledge is typical y passedfrom doctor to doctor.
The good news from this study is that the problem should be easy to correct. Ifnitric oxide is what is needed, it can be added to banked blood just beforetransfusion. As part of the project, Dr Stamler tried this with dogs. He foundthat old blood replenished with nitric oxide is as good as fresh blood at relaxingblood vessels. And that, he thinks, points to a bigger possibility than merelyreturning blood to normal. Blood boosted with nitric oxide might be used as atherapy for people who have had heart attacks by providing extra oxygen inthe crucial minutes after an attack, before the affected heart muscle has died.
At that point, blood transfusions would no longer be part of the problem: theywould be part of the cure.
It's a knockout
Oct 11th 2007
From The Economist print edition
Prizes for genetically disadvantaged mice,
computer hard drives and the basis of much
of industrial chemistry
THE award of the Nobel science prizes often brings blinking into the limelightpeople who have laboured unknown to the wider world. Seldom, though, isthere such a compel ing human story to go with the intel ectual one as that ofMario Capecchi, one of the winners of the medicine prize. His father was anairman who was killed in North Africa during the second world war. His motherwas sent to Dachau concentration camp. He survived more than three years asa street kid in Italy before migrating to America after the war was over — andyet he ended up helping to develop one of the most important tools of modernbiology, the knockout mouse.
It is not quite a rags-to-riches story. In truth, his family was wel connected ina bohemian sort of way, and his mother (the daughter of a painter and anarchaeologist) was an American. But it does make great copy for reporterscovering an event that has the true characteristics of celebrity. For, like manyof those who populate the pages of celebrity magazines, the Nobelprizewinners are most famous for being famous. In most years, theprize-winning work itself makes dull copy.
This year, however, the prize committees of the Karolinska Institute (Sweden'smain medical school) and the country's Royal Academy of Science seem tohave taken some lessons in public relations. Not only have they picked aresearcher with an interesting back-story, but they have also cunninglydisguised a deserved but possibly contentious award by bundling it in withsomething else. On top of that, one of the topics chosen for a prize has anobvious resonance with the public.
The bundling was done in the medicine prize. Dr Capecchi shares this withOliver Smithies, another immigrant to America (he was born in Britain) and SirMartin Evans, a Briton who stayed at home. Working independently, thesethree men provided the parts that, when put together, enable the eliminationof one gene at a time from the genetic make-up of a mouse. That is of medicalsignificance because it allows mouse “models” of human genetic diseases to bemade—and most diseases have at least some genetic component.
The contribution made by Dr Capecchi and Dr Smithies was to work out how todefine and excise particular pieces of DNA from a cel while leaving the restintact. It is Sir Martin's role, however, that is of most interest, for he discoveredwhat are now known as embryonic stem cel s and thus opened a field ofendeavour that has had political as wel as medical ramifications.
The first practical application of embryonic stem cel s was to provide a way forthe gene-targeting trick invented by Dr Capecchi and Dr Smithies to be used toproduce adult mice lacking particular genes — or knockout mice, as they arenow cal ed. You do this by crossbreeding mice that have had some of their cel streated this way when they were embryos, and have thus developed sex cellsthat lack the knocked-out gene. Certain of the offspring of these crosses wilinherit the lack of the gene in question from both parents, and thus it wil beentirely absent from them. That was what the Karolinska gave Sir Martin hisprize for. But although he discovered the cel s in mouse embryos, humanembryos have them too, and that is leading to trouble as the desires ofresearchers butt up against the fears of ethicists.
The physics prize, by contrast, has nothing but feel-good about it. It is for giantmagnetoresistance — the basis of modern computer hard-drive memories. Thephenomenon itself was discovered, independently, by Albert Fert, aFrenchman, and Peter Grünberg, a German, in 1988. Its significance is that asmall magnetic field can induce a large change in the electrical conductivity ofan appropriately designed material. (Appropriate design, in this context,means layers of different substances assembled in a way reminiscent ofmolecular puff pastry.) That means individual bits of data can be stored asmagnetic domains on a spinning disk, and the changes in conductivity theyinduce in a reading head held over the disk can be turned into signals that acomputer can process. The result has been that the amount of data computerscan store has grown even faster than their ability to process it. The discoverymade by Dr Fert and Dr Grünberg has thus out-Moored Moore's law.
Only the chemistry prize has preserved the traditional aura of obscurity. It goes to Gerhard Ertl, another German, and is for his studies of the role ofsurfaces in catalysing chemical reactions. Since an awful lot of industrialchemistry is catalysed this way, and the chemical industry lies, one way oranother, at the base of most manufacturing, there is a good argument that thisis the most important prize of the lot. But glamorous? Sadly not.
Blowing in the wind
Oct 11th 2007
From The Economist print edition
The building blocks of planets and people
come from black holes
WHEN the writer of Genesis said man was made of dust, he spoke true. Andnot just man. The whole Earth was made from dust particles in orbit aroundthe primitive sun, as were all the other solid objects in the solar system. Buthow did the dust itself come into existence? That is a puzzle. Modern space dust blows off stars that formed about 10 bil ionyears ago. These stars would have been too young to have shed much of thestuff by the time that the solar system formed, 4.5 billion years ago. Theuniverse's primordial dust must therefore have come from somewhere else —and a team of researchers led by Ciska Markwick-Kemper of the University ofManchester think they know where. The answer is from black holes.
The black holes in question are at the centres of quasars. These formed shortlyafter the universe began and they came to the attention of earthlingastronomers because quasars are powerful radio sources. The radio waves(and lots of other radiation) are the result of matter being drawn into the blackhole and releasing energy as it fal s. But not al this matter is swal owed. Someis baked, transformed and spat out again. It was this transformation thatinterested Dr Markwick-Kemper.
Suspecting that it might be the source of primordial dust, she recruited a spacetelescope called Spitzer to look at a quasar called PG 2112+059 in more detail.
Spitzer is tuned to pick up infra-red radiation — the sort of radiation emitted bydust that has been heated. And the details of the spectrum of infra-redradiation given off by a speck of dust wil betray its composition.
Dr Markwick-Kemper and her col eagues report their findings in a forthcomingedition of Astrophysical Journal Letters. The dust around PG 2112+059contains large quantities of rock-forming minerals, including crystal ine forms of silica (essentially, small sand grains), a form of aluminium oxide calledcorundum (better known on Earth as the principal ingredient of rubies andsapphires) and a form of magnesium oxide called periclase (which is present inmarble).
These minerals must have been produced by the quasar, Dr Markwick-Kemperargues, because their crystal structures would not survive long in the hostileconditions of outer space. Cosmic rays would zap them into an amorphous,glass-like state. Moreover, corundum and periclase have not been detected inspace dust before. Their association with the quasar is therefore strongevidence that this is the object that created them. A human being may stil bea handful of dust. But that dust has had an exciting history.
Hidden charms
Oct 11th 2007
From The Economist print edition
Lap dancers earn more when they are most
“BECAUSE academics may be unfamiliar with the gentlemen's club sub-culture,some background may be helpful to understand why this is an ideal setting forunderstanding real-world attractiveness effects of human female oestrus.” No doubt readers of The Economist are equal y unfamiliar with this sub-culture,but for Geoffrey Mil er of the University of New Mexico, who penned the wordsabove in a paper just published in Evolution and Human Behaviour, such clubsare a field site as revealing of human biology as the Serengeti is of the biologyof lions and antelopes. Dr Mil er is an evolutionary psychologist — and theauthor of the theory that the large brains of humans evolved to attract theopposite sex in much the same way that a peacock's tail does. His latest foray,into the flesh-pots of Albuquerque, is intended to investigate an orthodoxy ofhuman mating theory. This is that in people, oestrus — the outward signs ofovulation — has been lost, so that men cannot tel when women are fertile.
This theory is based on the idea that in evolutionary terms it benefits womento disguise when they are fertile so that their menfolk wil stick around al thetime. Otherwise, the theory goes, a man might go hunting for alternativemating opportunities at moments when he knew that his partner was infertileand thus that her infidelity could not result in children.
However, this should result in an evolutionary arms race between the sexes,as men evolve ever-heightened sensitivity to signs of female fertility. Dr Millerthought lap-dancing clubs a good place to study this arms race, because maledetection of female fertility cues would probably translate into an easilyquantifiable signal, namely dol ars earned. He therefore recruited some of thegirls into his experiment, with a view to comparing the earnings of those on thePil (whose fertility was thus suppressed) with those not on the Pil .
The results support the idea that if evolution has favoured concealed ovulationin women, it has also favoured ovulation-detection in men. The averageearnings per shift of women who were ovulating was $335. Duringmenstruation (when they were infertile) that dropped to $185 — about whatwomen on the Pil made throughout the month. The lessons are clear. Awoman is sexier when she is most fertile. And if she wishes to earn a goodliving as a dancer, she should stay off the Pill.

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